Extracellular vesicles and their potential role in atrial fibrillation-related thrombogenicity

Atrial fibrillation is a prevalent cardiac arrhythmia that significantly increases the risk of thrombus formation in the left atrial appendage of the heart and subsequent thromboembolism. The mechanisms by which atrial fibrillation promotes thrombus formation may involve elevated blood levels of procoagulant molecules. In recent years, extracellular vesicles have attracted growing attention as potential prothrombotic agents. Extracellular vesicles are lipid bilayer membrane-bounded particles released from cells as a response to physiological or pathological stimuli. Extracellular vesicles can facilitate accumulation of blood coagulation factors and they can contain tissue factor, the principal initiator of blood clotting. Measurement of extracellular vesicles in blood is challenging as they are delicate and heterogenous analytes, coexisting with other blood components that may interfere with the analysis. In this PhD project, methods for extracellular vesicle detection and characterization were tested, addressing preanalytical and analytical challenges with a particular focus on interference from lipoproteins. Furthermore, venous and left atrial appendage blood levels of components with a thrombogenic potential, including tissue factor-bearing extracellular vesicles, were evaluated in a group of atrial fibrillation patients and a control group.